Exploring the relationship between interphase gene positioning, transcriptional regulation and the nuclear matrix

2010 ◽  
Vol 38 (1) ◽  
pp. 263-267 ◽  
Author(s):  
Lauren S. Elcock ◽  
Joanna M. Bridger

Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories. Determining the factors that drive the spatial positioning of these territories within nuclei has caused much debate; however, in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally. These observations pose a number of questions: first, what is the function of this global organization and, secondly, is it representative of that occurring at a more local scale? During the course of this review, these questions will be considered, in light of the current literature regarding the role of transcription factories and the nuclear matrix in interphase genome organization.

Development ◽  
1961 ◽  
Vol 9 (4) ◽  
pp. 650-660
Author(s):  
Cyril V. Finnegan

In order better to evaluate results obtained in this laboratory concerning the responses of differentiating postneurula somite tissue to other mesoderm tissue placed in its immediate vicinity (Finnegan, unpublished), it was necessary to examine somite differentiation in situ. A qualitative examination of somite interphase nuclei of tail-bud and later stages was performed to note their morphological changes since it was assumed, as suggested by Briggs & King (1955), that such changes indicate cellular differentiation and, conversely, that absence of such changes indicates that the cells are not actively differentiating. Because of the possible role of the intercellular matrix in histogenesis (see Grobstein, 1954, 1959; and Edds, 1958) a study was made of the development in the somite of that portion of the intercellular matrix which is demonstrable histochemically with the periodic acid-Schirf (PAS) technique. The visual clarity of the results has been materially aided by the fluorescent Schiff reagent of Culling & Vassar (1961) which makes possible a fluorescent Feulgen and a fluorescent PAS reaction.


Author(s):  
Edward G. Fey

In the past few years, considerable advances have been made regarding the structure and function of the nuclear matrix. In the first half of this presentation, the field of nuclear matrix research will be summarized. Emphasis will be placed on those studies where molecular interactions are demonstrated in situ utilizing high resolution light and/or electron microscopy. Studies demonstrating the role of the nuclear matrix in DNA synthesis and replication, RNA transcription and processing, and the binding of matrix attachment regions to specific nuclear matrix proteins will be summarized.


2017 ◽  
Vol 30 (23) ◽  
pp. 9527-9537 ◽  
Author(s):  
In-Hong Park ◽  
Seung-Ki Min

On a subdaily time scale, the intensities of extreme precipitation are observed to increase with temperature at a rate exceeding water vapor constraints determined by the Clausius–Clapeyron (C-C) relationship. This so-called super C-C scaling has been suggested to occur as a result of 1) the statistical effect that involves the transition of precipitation types from stratiform to convective events and 2) the physical effect by which the convective process itself can overcome the thermodynamic limitation. This study examines these two mechanisms for the super C-C relationship using in situ observations in South Korea for a recent 35-yr period, focusing on the role of convective rainfall. Scaling results show that hourly extreme precipitation undergoes a transition from a C-C rate to a super C-C rate at around 20°C, supporting the statistical effect. The transition temperature observed in South Korea is, however, much higher than in European regions (12°C), which seems to be due to the climatologically lower frequency of convective events in South Korea than in Europe. Nevertheless, the threshold fraction of convective precipitation when the scaling transition starts to occur is found to very similar between two regions, around 0.2, indicating the important role of convective events in shaping the scaling. On the other hand, convective extreme precipitation alone exhibits a super C-C scaling, suggesting that the physical effect is also at work in South Korea. Also, the scaling shows a robust peaklike shape with maximum precipitation intensity near 24°C, which is closely linked with moisture limitation at high temperature, supporting the previous findings.


2004 ◽  
Vol 61 (21) ◽  
pp. 2544-2558 ◽  
Author(s):  
Kathleen K. Crahan ◽  
Dean A. Hegg ◽  
David S. Covert ◽  
Haflidi Jonsson ◽  
Jeffrey S. Reid ◽  
...  

Abstract Although the importance of the aerosol contribution to the global radiative budget has been recognized, the forcings of aerosols in general, and specifically the role of the organic component in these forcings, still contain large uncertainties. In an attempt to better understand the relationship between the background forcings of aerosols and their chemical speciation, marine air samples were collected off the windward coast of Oahu, Hawaii, during the Rough Evaporation Duct project (RED) using filters mounted on both the Twin Otter aircraft and the Floating Instrument Platform (FLIP) research platform. Laboratory analysis revealed a total of 17 species, including 4 carboxylic acids and 2 carbohydrates that accounted for 74% ± 20% of the mass gain observed on the shipboard filters, suggesting a possible significant unresolved organic component. The results were correlated with in situ measurements of particle light scattering (σsp) at 550 nm and with aerosol hygroscopicities. Principal component analysis revealed a small but ubiquitous pollution component affecting the σsp and aerosol hygroscopicity of the remote marine air. The Princeton Organic-Electrolyte Model (POEM) was used to predict the growth factor of the aerosols based upon the chemical composition. This output, coupled with measured aerosol size distributions, was used to attempt to reproduce the observed σsp. It was found that while the POEM model was able to reproduce the expected trends when the organic component of the aerosol was varied, due to large uncertainties especially in the aerosol sizing measurements, the σsp predicted by the POEM model was consistently higher than observed.


1995 ◽  
Vol 130 (6) ◽  
pp. 1239-1249 ◽  
Author(s):  
H Yokota ◽  
G van den Engh ◽  
J E Hearst ◽  
R K Sachs ◽  
B J Trask

We determined the folding of chromosomes in interphase nuclei by measuring the distance between points on the same chromosome. Over 25,000 measurements were made in G0/G1 nuclei between DNA sequences separated by 0.15-190 megabase pairs (Mbp) on three human chromosomes. The DNA sequences were specifically labeled by fluorescence in situ hybridization. The relationship between mean-square interphase distance and genomic separation has two linear phases, with a transition at approximately 2 Mbp. This biphasic relationship indicates the existence of two organizational levels at scales > 100 kbp. On one level, chromatin appears to be arranged in large loops several Mbp in size. Within each loop, chromatin is randomly folded. On the second level, specific loop-attachment sites are arranged to form a supple, backbonelike structure, which also shows characteristic random walk behavior. This random walk/giant loop model is the simplest model that fully describes the observed large-scale spatial relationships. Additional evidence for large loops comes from measurements among probes in Xq28, where interphase distance increases and then locally decreases with increasing genomic separation.


1990 ◽  
Vol 41 (5) ◽  
pp. 581 ◽  
Author(s):  
RL Oliver

Apparent and inherent optical properties were determined for a range of water types in the Murray- Darling basin by using a combination of field and laboratory techniques. The absorption coefficient was calculated directly from in situ irradiance measurements of photosynthetically active radiation, whereas the scattering coefficient was determined from the irradiance measurements in conjunction with published nomograms relating the apparent and inherent optical properties. The validity of the nomograms for use in these waters was confirmed by comparing values of the average cosine calculated directly from in situ measurements with those estimated from the nomograms. These were closely correlated except for sites with chlorophyll concentrations greater than 200 mg m-3. The scattering coefficients estimated from the nomograms were approximately numerically equal to the turbidity in nephelometric turbidity units, but the variability of the relationship made it unsuitable for checking the validity of the nomograms. The relative role of dissolved and particulate components in the absorption and scattering of irradiance was examined by using spectrophotometry and linear regression of inherent optical properties on concentrations of the components. Estimates of specific absorption and scattering coefficients for algae, non-chlorophyllous suspended particles, and dissolved yellow colour were comparable to similar coefficients reported in the literature. The relative importance of these components to absorption and scattering varied considerably between sites and demonstrated the need for information on inherent optical properties in understanding the factors causing changes in optical water quality.


1993 ◽  
Vol 265 (2) ◽  
pp. C397-C405 ◽  
Author(s):  
Z. A. Eppley ◽  
J. Kim ◽  
B. Russell

Myogenic regulatory factors (MRFs) induce differentiation in developing muscle. We examined the role of MRFs in the repair of adult muscle using a model of stretch-induced injury in 5-wk-old chickens. The anterior latissimus dorsi muscle was stretched by loading the wing with 10% of body weight, while the contralateral muscle served as a control. At various intervals (0.5-72 h), chickens were killed by CO2 asphyxiation and the muscles were frozen. Slot hybridizations showed that the onset of high qmf1 expression occurred as early as 0.5 h, which was before regenerative processes involving satellite cell proliferation were observed. Maximal qmf1 expression varied among animals from 3 to 16 h and returned to control levels by 72 h. Within a muscle, in situ hybridization showed that maximal qmf1 expression varied spatially with > 60% of the nuclei within active fascicles being positive. We interpret this high percentage to mean that many of the nuclei of preexisting muscle fibers must be expressing qmf1. The expression of the protooncogene c-myc (presumably by proliferating cells such as satellite cells, fibroblasts, and capillary epithelial cells) and the MRF qmf1 (by myoblasts and adult muscle nuclei) are among the early molecular responses of injured muscle. We conclude that myogenic regulatory factors are not permanently repressed after embryonic development and that derepression plays a role in the repair of terminally differentiated myofibers.


2020 ◽  
Vol 106 (6) ◽  
pp. NP67-NP72
Author(s):  
Ileana Carnevali ◽  
Eleonora Di Lauro ◽  
Valeria Pensotti ◽  
Nora Sahnane ◽  
Eleonora Leoni ◽  
...  

Introduction: The relationship between endocervical cancer and cancer susceptibility syndromes is not yet fully understood. We present 2 cases of endocervical cancer: 1 arising in a patient carrier with a pathogenic BRCA1 variant and the second detected in a Lynch syndrome family carrying the MSH2 germline pathogenic variant. Case description: Somatic analyses including loss of heterozygosity and fluorescent in situ hybridization demonstrated that the second hit in patient 1 is BRCA1-related. Mismatch repair somatic analyses in the second family demonstrated that the endocervical cancers of patient 2 and of her sister are MSH2-related. These data confirm the relationship between the pathogenesis of endocervical cancer and the presence of germline BRCA1 and MSH2 mutations. Conclusions: Our study confirms that gynecologic cancers including rare entities such as non–human papillomavirus–related endocervical cancer (NHPVA) are sentinels for inherited cancer syndromes. Endocervical cancer NHPVAs might be considered for cancer genetic counseling in order to improve cancer prevention. For this reason, the role of pathologists is particularly important for the correct identification of the cervical tumor site.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 434
Author(s):  
Heihachiro Nishimura ◽  
Hirokazu Fukui ◽  
Xuan Wang ◽  
Nobuhiko Ebisutani ◽  
Takashi Nakanishi ◽  
...  

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5860
Author(s):  
Concetta Federico ◽  
Francesca Bruno ◽  
Denise Ragusa ◽  
Craig S. Clements ◽  
Desiree Brancato ◽  
...  

The last decade has seen significant progress in understanding how the genome is organized spatially within interphase nuclei. Recent analyses have confirmed earlier molecular cytogenetic studies on chromosome positioning within interphase nuclei and provided new information about the topologically associated domains (TADs). Examining the nuances of how genomes are organized within interphase nuclei will provide information fundamental to understanding gene regulation and expression in health and disease. Indeed, the radial spatial positioning of individual gene loci within nuclei has been associated with up- and down-regulation of specific genes, and disruption of normal genome organization within nuclei will result in compromised cellular health. In cancer cells, where reorganization of the nuclear architecture may occur in the presence of chromosomal rearrangements such as translocations, inversions, or deletions, gene repositioning can change their expression. To date, very few studies have focused on radial gene positioning and the correlation to gene expression in cancers. Further investigations would improve our understanding of the biological mechanisms at the basis of cancer and, in particular, in leukemia initiation and progression, especially in those cases where the molecular consequences of chromosomal rearrangements are still unclear. In this review, we summarize the main milestones in the field of genome organization in the nucleus and the alterations to this organization that can lead to cancer diseases.


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